Dupilumab benefits in EoE sustained through 52 weeks
The anti–interleukin (IL)-4/-13 antibody dupilumab led to sustained improvements across symptomatic, histologic, and endoscopic measures of eosinophilic oesophagitis (EoE) out to 52 weeks, according to additional data from the LIBERTY EoE TREET trial presented at ACG 2021.
“EoE is a chronic type 2 inflammatory disease of the oesophagus, characterized by eosinophilic inflammation leading to symptoms of oesophageal dysfunction,” explained lead author Professor Evan Dellon from the University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, US.
This can lead to damage and pain in the oesophagus, which can cause swallowing difficulties and affect quality of life substantially.
“Current treatment options with PPI, topical corticosteroids and elimination diets lack specificity, present adherence challenges, and may offer suboptimal long-term disease control,” Dellon said.
In the double-blind, phase III study, 81 patients with EoE were randomized to receive subcutaneous dupilumab 300 mg weekly or placebo in a 1:1 ratio for 24 weeks. From this, 77 eligible patients who completed the double-blind phase entered into the 28-week extended treatment phase, whereby all participants received dupilumab up to 52 weeks. [ACG 2021, abstract 52]
At week 24, patients treated with dupilumab saw significant improvements from baseline in both the coprimary outcomes of peak oesophageal intraepithelial eosinophil count (least-squares [LS] mean, -71.24 vs -2.98; p<0.0001) and Dysphagia Symptom Questionnaire (DSQ) score (LS mean, -21.92 vs -9.60; p=0.0004) compared with those on placebo during the double-blind phase.
The clinical benefits persisted through 52 weeks in the extension phase, whereby the improvements in peak oesophageal intraepithelial eosinophil count (LS mean, -88.59) and DSQ score (LS mean, -23.44) were maintained in patients who were initially assigned to dupilumab and continued on-treatment.
“Placebo-treated patients from [the double-blind phase] who switched to dupilumab treatment in the [extension phase] showed similar efficacy to dupilumab-treated patients [seen in the double-blind period],” said Dellon. Patients who switched from placebo saw LS mean changes of -63.76 for eosinophil count and -21.71 for DSQ score.
Similarly, reduction in histologic severity — as indicated by absolute change in histology scoring system (HSS) mean grade score — was greater in the dupilumab group than the placebo group (LS mean, -0.761 vs -0.001; p<0.001) at week 24. The improvement continued through week 52 during the extension phase in the dupilumab group (LS mean, -0.87) as well as in those who switched from placebo to dupilumab (LS mean, -0.87).
Improvement in histologic extent — as indicated by absolute change in HSS mean stage score — was also greater in the dupilumab group at week 24 (LS mean, -0.753 vs -0.012; p<0.001), which persisted to week 52 (LS mean, -0.89). Again, the placebo-to-dupilumab group saw similar improvement at week 52 (LS mean, -0.87).
In terms of endoscopic improvement, dupilumab significantly reduced endoscopic features of EoE compared with placebo, as assessed by changes endoscopic reference score (EREFS) from baseline to week 24 (LS mean, -3.2 vs -0.3; p<0.001). At week 52, the improvement was sustained in the dupilumab group (LS mean, -4.1) while the placebo-to-dupilumab group achieved similar outcome (LS mean, -3.9).
“In this phase III study, dupilumab vs placebo demonstrated statistically significant and clinically meaningful improvements across symptomatic, histologic, and endoscopic domains of EoE at week 24, which were sustained to week 52,” Dellon summed up.
“Dupilumab was generally well tolerated, with a low incidence of serious adverse events and adverse events leading to discontinuation,” he reported.